In a normal cardiac physiology, the human heart consists of two ventricles or pumping chambers. As depicted in FIG. 1A, the left ventricular (LV) chamber drives blood through the body and end-organs via the aorta (Ao), while the right ventricle (RV) pumps blood to the lungs for gas exchange via the left pulmonary artery (LPA) and the right pulmonary artery (RPA).
Whether as a result of acquired or congenital heart disease, failure of the cardiovascular system is a progressive and debilitating disease that affects tens of millions of people worldwide. In the U.S., approximately 7 million people suffer from heart failure and hundreds of thousands of new cases are diagnosed each year. This costs the healthcare industry tens of billions annually, and only a few thousand donor hearts are available each year. Thousands are registered awaiting a donor heart, with many patients dying while on the waiting list.
In addition, thousands of infants, however, are born each year with abnormal cardiac physiology due to congenital heart defects and cardiac structural disorders. The incidence of congenital heart defects is reported to be approximately 4-10 of every 10,000 live births in the United States. Those defects having the highest complexity, such as hypoplastic left heart syndrome and tricuspid atresia, lead to a single ventricle physiology, requiring invasive heart surgery in the first year of life. These patients utilize healthcare resources disproportionate to their numbers with treatment costs exceeding $1.4 billion annually.
Patients exhibiting a single ventricle physiology typically undergo three staged palliative cardiac surgeries. Each surgery progressively offloads the single ventricle while allowing time for growth, development, and adaptation to the altered physiology. The Fontan procedure is the final surgical stage providing separation of the pulmonary and systemic circulations and creation of the total cavopulmonary connection (TCPC) where the inferior vena cava (IVC) and superior vena cava (SVC) are joined directly to feed the pulmonary arteries. In contrast to a normal cardiophysiology having two main pumping chambers (ventricles), a Fontan physiology has only one single ventricle to drive and draw blood flow through both the systemic and pulmonary circulations. In this anatomic configuration depicted in FIG. 1B, blood flows passively from the venous system into the lungs without a subpulmonary power source or right ventricle to provide the requisite pressure boost to push blood to the left atrium (LA). This total cavopulmonary connection (TCPC) is analogous to fluid flow in a four-way intersection with 2 offset inputs (SVC and IVC) and 2 primary outputs (left and right pulmonary arteries) in a cross-like orientation. After the Fontan procedure, elevated central venous pressures have been linked to mounting complications, including liver disorders, cardiac arrhythmias, and thrombosis, or clot formations. Few therapeutic alternative treatments exist, except for a heart transplant if the patients can survive the waiting period. Clinically-approved blood pumps or ventricular assist devices (VADs) are not ideal treatment options because these are designed for patients with normal anatomy and heart failure, not for patients having dysfunctional or failing Fontan physiology.
The treatment of single ventricle anomalies represents a formidable challenge for clinicians caring for patients with congenital heart disease. The incidence of children born with a single ventricle heart is about 2 per 1000 births. Over their lifespan, these patients utilize healthcare resources disproportionate to their numbers. Hospitalization costs exceed $1.4 billion per year for this cohort of patients and constitute an emerging public health concern. These patients live with a near compromised circulatory status due to their unique, anatomic cardiophysiology. As a result, individuals with a univentricular Fontan circulation are at high risk of developing complications of systemic venous hypertension, thromboembolism, and CHF. Approximately 25% of the 1st generation of Fontan recipients will develop heart failure within 15 years, while the 2nd generation appears to be living longer with 87% surviving to 10 years. Heart transplantation for these patients is a treatment option if they can be stabilized and survive the organ waiting period. Only modest improvements in outcomes of surgical repair have been achieved. In an effort to improve stability and survival, mechanical support strategies have been increasingly applied. Currently available ventricular assist devices (VADs), however, are designed for use in unhealthy biventricular circulations, not single ventricle configurations.